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[Autoimmune enteropathy causing protracted diarrhea]. Naveh Y,Ben-Arieh Y,Greif Z,Berant M Harefuah A 3-month old female infant was transferred from another hospital where she had been hospitalized from the age of 1 month for protracted secretory diarrhea. The diarrhea had begun at birth and was unresponsive to various therapeutic formulas and to total parenteral nutrition (TPN). The parents were consanguineous. There were 6 normal siblings, while 3 siblings had died in infancy, including a sister who had succumbed to protracted diarrhea at the age of 6 months. In our patient duodenal biopsy showed flattening of villi and proliferation of mononuclear cells in the lamina propria. Specific circulating IgG antibodies against gut epithelium were found, as well as thyroglobulin antibodies. Repeated trials of oral feeding were unsuccessful and TPN was required for 8 months. Complications included septicemia, osteomyelitis and acute renal failure. Therapeutic trials with intravenous hydrocortisone, zinc sulphate and metronidazole were unsuccessful and the infant died at the age of 11 months. Intestinal tissue taken postmortem showed nearly absolute flattening of intestinal villi. This is the first report in Israel of intractable infantile diarrhea due to autoantibodies to intestinal epithelium.
Autoimmunity in diarrhoeal disease. Unsworth D J,Walker-Smith J A Journal of pediatric gastroenterology and nutrition Evidence for autoimmunity in diarrhoeal disease is reviewed. Firstly, coeliac disease (CD) is considered. The incidence of tissue-reactive autoantibodies in both adults and children with CD (68% and 65%, respectively) is higher than the incidence of these autoantibodies in controls (6% in normal adults, and 14% and 9% in disease controls drawn respectively from adult and child populations). The R1 antireticulin antibody, when present, was found to disappear after several weeks on a gluten-free diet, but in contrast, other autoantibodies persisted. Secondly, a case is argued for a new disease category, namely "autoimmune enteropathy." Seven cases are reviewed in which patients presented with protracted diarrhoea, a small intestinal enteropathy which failed to heal during periods of total parenteral nutrition, and evidence of a predisposition to autoimmunity (namely, the presence of high titre autoantibodies including one specific for gut epithelium, and/or the presence of associated diseases regarded to be autoimmune). Thirdly, evidence for autoimmunity in inflammatory bowel disease is reviewed and includes discussion of serum goblet cell antibodies and of circulating T cells which participate in antibody-dependent cellular cytotoxicity in vitro using colonic epithelial cells as targets. Finally, an unusual child is described who presented with chronic diarrhoea and a flat small intestinal mucosa, who responded to gluten withdrawal but who later relapsed spontaneously during a strict gluten-free diet. Her mucosa healed only after a period of total parenteral nutrition and treatment with oral steroids. This child's enteropathy was also associated with thyrotoxicosis and a microscopic colitis.
[Autoimmune enteropathy--difficulties in diagnosis and treatment]. Popińska K,Lyszkowska M,Ksiazyk J,Kierkuś J,Socha J Pediatria polska We describe a 42-month-old child with protracted diarrhoea that began at 6 months of age. Severe secretory diarrhoea persisted despite therapy with exclusion diets, total parenteral nutrition, chemotherapeutics, antisecretory drugs. The diagnosis of autoimmune enteropathy with total villous atrophy and anti-enterocyte antibodies was established at 16 months of age. Prednisone therapy induced a clinical remission. After dose reduction, clinical relapse occurred, complicated with HCV infection with elevated serum alanine aminotransferase activity. Increasing the prednisone dose did not result in clinical improvement. Treatment with cyclosporine induced clinical remission. After 10 months cyclosporine therapy is still continued and the boy is doing well.
[Autoimmune enteropathy]. Lachaux A Archives de pediatrie : organe officiel de la Societe francaise de pediatrie Autoimmune enteropathy was initially described in young male infants presenting as severe secretory diarrhea. The disease is characterized by an inflammatory reaction which may involve several organs (bowel, pancreas, thyroid, kidneys, liver) with the presence of various circulating antibodies. The disease may also be observed in older children and in females with usually less bowel involvement. In view of the autoimmune basis of the disease, treatment requires immunosuppressive agents in addition to parenteral nutrition.
Autoimmune enteropathy and villous atrophy in adults. Corazza G R,Biagi F,Volta U,Andreani M L,De Franceschi L,Gasbarrini G Lancet (London, England) BACKGROUND:Autoimmune enteropathy is a condition described in children and characterised by villous atrophy, which is unresponsive to any dietary restrictions, and by the presence of enterocyte autoantibodies. We report two adult patients who fulfilled all the criteria for the diagnosis of this disorder. METHODS:Over the past 5 years we have seen four adult patients (all women, median age 51.5 [range 38-64] years) with subtotal villous atrophy, which was unresponsive to a gluten-free diet. The patients were HLA-DQ2 positive. IgA antigliadin and antiendomysial antibodies were not found in any of the patients. We did an indirect immunofluorescence search for enterocyte autoantibodies on monkey jejunum and for other autoantibodies for all four patients. FINDINGS:Of the four patients, two were positive for enterocyte autoantibodies and one of these two patients was positive for antiactin, antiparietal cell, and antithyroid microsomal autoantibodies. INTERPRETATION:To the best of our knowledge the two patients affected by severe enteropathy, who had never responded to any exclusion diet, and who were positive for enterocyte autoantibodies are the first cases of autoimmune enteropathy described in adults. We propose that adult patients whose disorders are unresponsive to a gluten-free diet should be tested for enterocyte autoantibodies. 10.1016/S0140-6736(97)01042-8
Autoimmune enteropathy with goblet cell antibodies. Carr C S,Alkhulaifi A M Journal of the Royal Society of Medicine 10.1177/014107689909201030
Adult autoimmune enteropathy treated successfully with tacrolimus. Daum Severin,Sahin Ergün,Jansen Andreas,Heine Bernhard,Riecken Ernst-Otto,Zeitz Martin,Schmidt Wolfgang Digestion BACKGROUND:Autoimmune enteropathy is a life-threatening, chronic disease of the small bowel mucosa, which generally responds well to steroids. Treatment requires long-term immunosuppression, and steroid-sparing treatment strategies are desirable. Azathioprine and cyclosporine A have limitations, however alternatives have not been described in adults. CASE REPORT:We present the case of a 54-year-old male patient with autoimmune enteropathy who responded initially to a standard treatment with steroids, but was dependent on 30 mg prednisolone. Medical treatment was changed to tacrolimus after renal function deteriorated under treatment with cyclosporine A. Under this regimen, small bowel histology normalized and the clinical condition is stable after 2 years of introduction of tacrolimus. CONCLUSION:This constitutes the first report of effective treatment of adult autoimmune enteropathy with tacrolimus, a substance with a similar mode of action to cyclosporine, but with fewer side effects and improved bioavailability. 10.1159/000074520
Enteropathy with loss of enteroendocrine and paneth cells in a patient with immune dysregulation: a case of adult autoimmune enteropathy. Al Khalidi Hisham,Kandel Gabor,Streutker Cathy J Human pathology Autoimmune enteropathy (AIE) is a relatively rare condition found most frequently in children. It presents with persistent watery diarrhea and malabsorption and may require total parenteral nutrition for nutritional support. Rare cases have been reported in adults. On histology, the small intestinal villi are flattened but lack the intraepithelial lymphocytosis of celiac disease. In children and rarely in adults, some cases are linked to the IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked inheritance). We report a 21-year-old man who presented with chronic persistent diarrhea for 4 years. The duodenal biopsies showed villous blunting, chronic inflammation, and decreased to absent goblet cells, Paneth cells, and endocrine cells by histology and electron microscopy. These changes are consistent with an AIE with involvement of non-enterocyte populations. Pathologists must be aware of the possibility of AIE in adults and consider it in the differential diagnosis of duodenitis, intraepithelial lymphocytosis, and small bowel villous flattening. 10.1016/j.humpath.2005.11.019
Adult autoimmune enteropathy: Mayo Clinic Rochester experience. Akram Salma,Murray Joseph A,Pardi Darrell S,Alexander Glenn L,Schaffner John A,Russo Pierre A,Abraham Susan C Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association BACKGROUND & AIMS:Autoimmune enteropathy is a rare cause of intractable diarrhea associated with circulating gut autoantibodies and a predisposition to autoimmunity. It is rarely observed in adults, with only 11 cases reported to date. METHODS:Fifteen adults with autoimmune enteropathy were identified at the Mayo Clinic, Rochester, from May 2001-June 2006. The demographic, clinical, and treatment data were abstracted from their records. RESULTS:The study population was 87% white, 47% female, with median age of 55 years (interquartile range, 42-67 years). All patients had protracted diarrhea, weight loss, and malnutrition. Celiac disease was excluded by lack of response to gluten-free diet or absence of the celiac disease susceptibility HLA genotypes. Fourteen patients were tested for gut epithelial cell antibodies, and 93% were positive for anti-enterocyte and/or anti-goblet cell antibodies. Predisposition to autoimmune diseases was noted in 80%, as indicated by a variety of circulating autoantibodies. Small intestinal histopathologic findings included subtotal villous atrophy and lymphoplasmacytic infiltration in the lamina propria with relatively few surface intraepithelial lymphocytes. T-cell receptor gene rearrangement studies were negative in all cases. Immunosuppressive therapy was required in 93% of cases. Clinical improvement was noted in 60% after 1-8 weeks of steroid therapy. CONCLUSIONS:Autoimmune enteropathy is a heterogeneous disease and should be considered in the differential diagnosis of malabsorption and small bowel villous atrophy. The presence of gut epithelial cell antibodies can help confirm the diagnosis. No single agent is unequivocally effective in inducing remission, and immunosuppressive therapy is required in most cases. 10.1016/j.cgh.2007.05.013
Adult autoimmune enteropathy. Freeman Hugh-James World journal of gastroenterology Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti-enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet. 10.3748/wjg.14.1156
Autoimmune enteropathy in children and adults. Montalto Massimo,D'Onofrio Ferruccio,Santoro Luca,Gallo Antonella,Gasbarrini Antonio,Gasbarrini Giovanni Scandinavian journal of gastroenterology Autoimmune enteropathy is a rare disorder characterized by severe and protracted diarrhea, weight loss from malabsorption and immune-mediated damage to the intestinal mucosa, generally occurring in infants and young children, although some cases of adult onset have been reported in the literature. Pathogenetic mechanisms involve immunological disorders, in which the presence of antienterocyte autoantibodies, although detected since first description, seems now to be secondary. As occurs frequently in autoimmunity, subjects with autoimmune enteropathy may be affected by other autoimmune disorders, sometimes leading to particular forms, i.e. the IPEX syndrome and the APECED syndrome. The prognosis of autoimmune enteropathy patients depends on the severity of digestive symptoms (including fecal output), on the severity and extension of histological lesions along the gastrointestinal apparatus, and on the presence of extra-intestinal involvement. Management of autoimmune enteropathy patients is based on nutritional support and adequate hydration to ensure optimal growth and development, together with immunosuppressive therapy. Recently, biological agents have been introduced, with apparent beneficial effects. 10.1080/00365520902783691
Anti-goblet cell antibodies for the diagnosis of autoimmune enteropathy? Biagi Federico,Bianchi Paola I,Trotta Lucia,Corazza Gino R The American journal of gastroenterology 10.1038/ajg.2009.511
[Autoimmune enteropathy in an adult patient]. Piñero Pérez Concepción,Velasco Guardado Antonio,Fernández Pordomingo Alejandra,Tejedor Cerdeña María,Prieto Vicente Vanesa,Alvarez Delgado Alberto,Sánchez Garrido Ana,Prieto Bermejo Beatriz,Martínez Moreno Juan,Geijo Martínez Fernando,Blanco Muñez Oscar,Rodríguez Pérez Antonio Gastroenterologia y hepatologia Autoimmune enteropathy (AIE) is an infrequent cause of malabsorption that is usually associated with the presence of circulating autoantibodies and a predisposition to autoimmune disorders. This disease is more frequent in children. The diagnosis of this disorder is based on five criteria: chronic diarrhea (>6 weeks), malabsorption, specific histological findings, exclusion of similar disorders, and the presence of specific antibodies such as anti-enterocyte and anti-goblet cell antibodies. We present the case of a 63-year-old patient with chronic diarrhea, weight loss and significant deterioration of nutritional status. 10.1016/j.gastrohep.2010.09.002
[Autoimmune enteropathy in children]. Moes Nicolette D,Ruemmele Frank M,Rings Edmond H H M Nederlands tijdschrift voor geneeskunde Autoimmune enteropathy is a rare syndrome which, in children in its most severe form, causes severe life-threatening diarrhoea and dehydration. The enteropathy seems to be part of a systemic disorder that can include neonatal diabetes mellitus, haematological abnormalities, severe allergies and eczema. The syndrome characterised by 'immuno-dysregulation, polyendocrinopathy, autoimmune enteropathy, X-linkage' (IPEX syndrome) is the most severe and also the best characterised form of autoimmune enteropathy. Recently, more has been discovered about the pathophysiology of autoimmune enteropathy. It would seem that an immunological defect exists, which is caused by the non-functioning of regulatory T cells. Characteristic of this disorder are circulating auto-antibodies that cause destruction of the intestinal wall. In a number of patients, this defect is caused by mutations in the Foxp3 gene on the X chromosome. The discovery of the molecular background for autoimmune enteropathy provides important new potential opportunities for diagnosis and therapy. Treatment options for this condition are immunosuppression and bone marrow transplantation.
Enteropathy-associated T-cell lymphoma complicating an autoimmune enteropathy. Malamut Georgia,Verkarre Virginie,Callens Céline,Colussi Orianne,Rahmi Gabriel,MacIntyre Elizabeth,Haïoun Corinne,Meresse Bertrand,Brousse Nicole,Romana Serge,Hermine Olivier,Cerf-Bensussan Nadine,Cellier Christophe Gastroenterology Enteropathy-associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma frequently associated with celiac disease. We report a case of EATL complicating adult autoimmune enteropathy (AIE). Analysis of phenotype, rearrangements in T-cell receptor genes, and chromosome alterations by high-resolution comparative genomic hybridization identified features distinct from those described for types I and II EATL. Furthermore, EATL arose from a single T-cell clone that had been present for several years in AIE-associated, oligoclonal, intestinal T-cell infiltrate. Emerging T-cell clones should be monitored in patients with AIE who receive long-term immunosuppressive therapy. 10.1053/j.gastro.2011.12.040
Autoimmune enteropathy: a review and update of clinical management. Gentile Nicole M,Murray Joseph A,Pardi Darrell S Current gastroenterology reports Autoimmune enteropathy (AIE) is a rare condition characterized by intractable diarrhea, histologic changes on small intestinal biopsy, and failed response to dietary manipulation that also may present with extraintestinal manifestations. In many patients, immunosuppressive therapies are necessary. Although AIE is more common in infants, adult involvement has also been documented. Much of what is known about AIE has been gathered from case reports and small case series; therefore, more research in this evolving field is needed. IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) and APECED (autoimmune phenomena, polyendocrinopathy, candidiasis, and ectodermal dystrophy) are systemic forms of AIE. 10.1007/s11894-012-0276-2
Abatacept: a new treatment option for refractory adult autoimmune enteropathy. Gupta Nitin K,Yilmaz Omer,Fisher Mark,Yajnik Vijay Journal of clinical gastroenterology Autoimmune enteropathy (AIE) is a rare disease that has been observed in both children and adults. It typically manifests with symptoms of diarrhea, requiring long-term immunosuppression. Endoscopically, the duodenum typically exhibits villous blunting with partial or complete villous blunting, deep crypt lymphocytosis, increased apoptotic bodies, and minimal intraepithelial lymphocytosis on histologic analysis. The pathophysiology of AIE likely involves a hyperactive immune state in the setting of a T-cell regulatory defect, resulting in destruction of the enterocyte. We report a case of a 49-year-old woman who presented with refractory diarrhea, diagnosed as AIE. After failing multiple conventional therapies, she demonstrated clinical and histologic response to abatacept, a selective modulator of T-cell activation. We aim to increase awareness of this rare inflammatory disorder and new treatment options for this debilitating condition. 10.1097/MCG.0b013e3182a4e0ec
Autoimmune enteropathy in a 13-year-old celiac girl successfully treated with infliximab. Valitutti Francesco,Barbato Maria,Aloi Marina,Marcheggiano Adriana,Di Nardo Giovanni,Leoni Stefania,Iorfida Donatella,Corazza Gino R,Cucchiara Salvatore Journal of clinical gastroenterology Autoimmune enteropathy (AIE) is a rare cause of small bowel villous atrophy, characterized by malabsorption, unresponsiveness to dietary restriction, circulating autoantibodies to enterocytes, and an overall predisposition to autoimmunity. Albeit mainly regarded as a disease of early childhood, several adult-onset AIE cases have been identified. This report describes for the first time the life-threatening clinical presentation and the management of overlapping AIE in a compliant-to-diet young celiac girl. A 13-year-old celiac girl was admitted because of vomiting, weight loss, diarrhea, hypoproteinemia, and neurological disturbances such as head tremors, vertical nystagmus, and lower limb hyperesthesia. Before this, she had always been compliant on a strict gluten-free diet and her medical history was unremarkable. The diagnosis of AIE was established on histologic findings and on the presence of antienterocyte antibodies. She was initially treated with high-dose Methylprednisolone and Azathioprine. However, only Infliximab proved itself as a highly effective tool for achieving clinical remission and restoring small bowel villous architecture. 10.1097/MCG.0b013e31829e460e
Glutamine-supplemented parenteral nutrition and probiotics in four adult autoimmune enteropathy patients. Xu Ren Ying,Wan Yan Ping,Zhou Yi Quan,Lu Li Ping,Chen Zhi Qi,Wu Ying Jie,Cai Wei Gut and liver To evaluate the effects of glutamine-supplemented parenteral nutrition (PN) and probiotics in adult autoimmune enteropathy (AIE) patients. Four adult AIE patients were identified from April 2006 to January 2012. Clinical and nutritional data were obtained from the patients' medical records. Glutamine-supplemented PN started immediately when the AIE diagnosis was confirmed. The total PN duration was 351 days. According to the PN prescription, the average caloric intake ranged from 20 to 25 kcal/kg/day, and the protein intake ranged from 1.2 to 1.5 g/kg/day. Alanyl-glutamine (20 g/day) was administered to AIE patients for 4 weeks followed by a 2-week break, and this treatment schedule was repeated when PN lasted for more than 6 weeks. Body weight gain and an increased serum albumin level were achieved after PN, and defecation frequency and quality also improved. Each patient received oral supplements, 250 mL of Ensure and two probiotics capsules (each capsule containing 0.5×108 colonies) three times a day when enteral nutrition started. Three AIE patients were successfully weaned off PN, and one patient died of pneumonia. Glutamine-supplemented PN and probiotics show promise in managing patients with AIE and related malnutrition. 10.5009/gnl.2014.8.3.324
Chronic diarrhea because of villous atrophy unrelated to celiac disease. van Lent Anja Ursula,Takkenberg R Bart,van Eeden Susanne,Mulder Chris,Beuers Ulrich Endoscopy 10.1055/s-0034-1391247
[Autoimmune enteropathy]. Kinnunen Urpo,Vuopala Katri,Kaukinen Katri Duodecim; laaketieteellinen aikakauskirja Autoimmune enteropathy (AIE) is characterized by protracted diarrhea, malabsorption, immunomediated damage to the intestinal mucosa, and unresponsiveness to changes in diet. The disease is mainly manifested in the small intestine. Lymphocyte deposits are present on the mucous membrane, and anti-enterocyte or anti-goblet cell antibodies have been described in the majority of affected persons. AIE occurs primarily in infants. Immunosuppressive drugs have been used with varying success. The prognosis of AlE is dependent on the degree of severity of the damage to the intestinal mucosa and extraintestinal symptoms and diseases associated therewith.
A Difficult and Rare Diagnosis of Autoimmune Enteropathy in a Patient Affected by Down Syndrome. Depince-Berger Anne,Cremilieux Clara,Rinaudo-Gaujous Melanie,Genin Christian,de Freminville Benedicte,Lambert Claude,Bruneau J,Paul Stephane Journal of clinical immunology Patients with Down syndrome are more susceptible to autoimmune pathologies, in particular endocrine or digestive diseases such as celiac disease. Autoimmune enteropathy is another form of digestive autoimmune disease, non-gluten-dependant, more often diagnosed in male neonates with immunodysregulation and polyendocrinopathy such as the Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome. It also exists in the adult, but this pathology is less known and therefore frequently under-diagnosed. Clinical manifestations are similar to celiac disease, but not improved after a gluten-free diet. Autoimmune enteropathy is frequently associated with other autoimmune diseases, such as thyroiditis, myasthenia gravis, lupus or immune deficiencies, as Common Variable Immunodeficiency. Pathological analysis of intestinal biopsies can frequently distinguish autoimmune enteropathy and celiac disease. Autoimmune enteropathy usually has an important lymphoplasmacytic infiltration of the mucosa and a lack of intraepithelial lymphocytes in the gastrointestinal mucosal surface, while celiac disease usually has a polymorph infiltration of the mucosa and an important intraepithelial lymphocytes infiltration. Nevertheless, the two pathological patterns may overlap. Here we report the first case of a patient with Down syndrome associated to autoimmune enteropathy (initially diagnosed as celiac disease), chronic pancreatitis and cutaneous lupus erythematosus. Even if autoimmune pathologies are much more common in patients with Down syndrome, we would like to report on this rare and original association found in our patient. 10.1007/s10875-016-0280-7
Autoimmune enteropathy: not all flat mucosa mean coeliac disease. Volta Umberto,Mumolo Maria Gloria,Caio Giacomo,Boschetti Elisa,Latorre Rocco,Giancola Fiorella,Paterini Paola,De Giorgio Roberto Gastroenterology and hepatology from bed to bench A 62-year-old woman complaining of severe malabsorption was diagnosed with celiac disease based on the findings of flat, small intestinal mucosa and HLA-DQ2 positivity, although celiac serology was negative. This diagnosis was questioned due to the lack of clinical and histological improvement after a long period of strict gluten-free diet. The detection of enterocyte autoantibodies guided to the correct diagnosis of autoimmune enteropathy, leading to a complete recovery of the patient following an appropriate immunosuppressive treatment. Autoimmune enteropathy should be considered in the differential diagnosis of malabsorption with severe villous atrophy, including those cases with negative celiac-related serology.
Seronegative Adult Autoimmune Enteropathy in a Male Traveler. McCabe Patrick,Alli-Akintade Latifat,Stondell Jesse ACG case reports journal Autoimmune enteropathy (AIE) is rare but damaging. The lack of consistent objective findings makes diagnosis a challenge. A 45-year-old male developed noninfectious diarrhea with significant weight loss and electrolyte abnormalities. Computed tomography delineated enteritis. Colonoscopy and esophagogastroduodenoscopy showed villous atrophy, chronic inflammation, and ulceration of the terminal ileum and cecum. Pathology showed cryptitis with apoptosis and abscesses throughout the small and large bowel and absent goblet cells. Steroids rapidly improved symptoms. Anti-enterocyte antibody serologies were negative. Management can be challenging, and, in this case, the patient initially improved with budesonide and infliximab but required alternative anti-tumor necrosis factor therapy after relapsing. This is an unusual presentation of seronegative AIE, which should be considered in cases of persistent severe diarrhea. 10.14309/crj.2017.19
[Severe diarrhoea due to autoimmune enteropathy: Treatment and outcomes]. Lázaro de Lucas Carmen,Tesouro Rodríguez Laura,Magallares García Lorena Nélida,Martínez-Ojinaga Nodal Eva,Ramos Boluda Esther Anales de pediatria 10.1016/j.anpedi.2017.06.009
Autoimmune enteropathies. Umetsu Sarah E,Brown Ian,Langner Cord,Lauwers Gregory Y Virchows Archiv : an international journal of pathology Autoimmune enteropathy (AIE) is a rare condition characterized by intractable diarrhea and immune-mediated injury of the intestinal mucosa. As the clinical and histopathologic manifestations of this disease are highly variable, its diagnosis is challenging for both clinicians and pathologists. In fact, the term autoimmune enteropathies is likely more appropriate since the clinicopathologic manifestations are observed in association with a heterogeneous group of disorders. The pathophysiology of AIE has not been fully elucidated. It appears to result from dysregulation of intestinal immunity and particularly in children, often presents in association with immunodeficiency. The overarching histopathologic changes seen in AIE include mucosal inflammation and epithelial injury, although this can manifest in the form of different patterns. Recognition of the clinical settings and of the various histologic patterns can aid the pathologist in establishing the correct diagnosis. 10.1007/s00428-017-2243-7
Autoimmune Enteropathy: An Updated Review with Special Focus on Stem Cell Transplant Therapy. Ahmed Zunirah,Imdad Aamer,Connelly James A,Acra Sari Digestive diseases and sciences Autoimmune enteropathy (AIE) is a complex disease affecting both children and adults. Although associated with significant morbidity and mortality, the pathophysiology of the disease and its treatment have not been well characterized. This study aims to review the medical literature available on this rare but clinically significant ailment, to help establish a better understanding of its pathophysiology and enumerate the available diagnostic and treatment modalities. A literature search was conducted on PubMed using key terms related to autoimmune enteropathy and intractable diarrhea, with no restrictions on the date of publication or language. We found a total of 98 reports of AIE published in the form of case reports and case series. The evidence reviewed suggests that AIE is a multifaceted disorder that requires a high index of suspicion in the appropriate clinical setting to be able to make an early diagnosis. Current evidence supports the use of supportive care to correct nutritional and metabolic deficiencies, and immunosuppressives and immunomodulators as directed therapies. Hematopoietic stem cell transplant is an aggressive, but successful curative modality for patients with AIE as part of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Cumulative clinical experience with management of AIE has allowed improved outcomes in transplanted and non-transplanted AIE patients even though morbidity and mortality with are still high in patients with this condition. More research is needed to further define the role of new therapies for AIE, and a central registry with participation of multiple institutions might help share and standardize care of patients with this rare but serious condition. 10.1007/s10620-018-5364-1
A man in his fifties with chronic diarrhoea and weight loss. Sarna Vikas Kumar,Lunding Johan,Løberg Else Marit,Solberg Inger Camilla Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke BACKGROUND:Watery diarrhoea coupled with weight loss is a serious condition with many potential causes. We present a possibly underappreciated cause which usually responds well to treatment; left untreated it may have a severe course. CASE PRESENTATION:A man in his fifties with known coronary and cerebrovascular disease was admitted for watery diarrhoea. Prerenal kidney failure occurred on the same day as the initial colonoscopy. The next day he suffered a stroke. He was anticoagulated and recovered within days. In the following months his state of malabsorption continued, with ultimately 50 % weight loss (BMI 14.7) and severe electrolyte disturbances. Intravenous electrolyte solutions and nutrition were administered. Oedema and aphthous duodenal lesions were the only endoscopic findings. Microscopic findings of total villus atrophy in all sampled sites in the small intestine, including the ileum, were striking. There were inflammatory cells in lamina propria, apoptotic cells and disappearance of goblet cells. Coeliac disease was ruled out by serology and HLA typing. INTERPRETATION:A final diagnosis of autoimmune enteropathy was made, based on exclusion of other intestinal and systemic diseases. Treatment with infliximab intravenously and budesonide in an open capsule regime was successful. 10.4045/tidsskr.19.0812
Isolated Intestine Transplantation for Autoimmune Enteropathy: A Case Report. Soma Daiki,Saxena Romil,Arman Mehmet E,Mihaylov Plamen,Ekser Burcin,Kubal Chandrashekhar A,Mangus Richard S Transplantation proceedings Autoimmune enteropathy is a rare disease characterized by chronic watery diarrhea, weight loss, and immune-mediated injury of the enterocolic mucosa. The clinicopathologic findings of this disease are variable, and timely diagnosis is challenging. It is usually managed medically. If medical management fails, surgical intervention is considered. This is a case report of a patient with autoimmune enteropathy mimicking collagenous enterocolitis. A 55-year-old man developed intestinal failure that manifested as profuse watery diarrhea, electrolyte disturbances, and weight loss. Initially, he was diagnosed with collagenous enterocolitis based on pathologic findings. Medical interventions were started, but the patient failed to show improvement. At 13 months after the onset of the disease, he was listed for isolated intestine transplantation (IITX) for intestinal failure. A healthy donor graft became available. IITX with chimney colostomy was performed. Based on the pathologic findings of the excised native small intestine, the patient was diagnosed with severe autoimmune enteropathy. The postoperative course was uneventful. By the third postoperative week, a full diet was tolerated and parenteral nutrition (PN) was weaned to end. He was discharged on postoperative day 34. Since discharge, he has been off PN, remaining on an enteral diet. This case is the first reported IITX performed on a patient with severe autoimmune enteropathy that was both curative and lifesaving. The present case confirms that IITX promptly restores gastrointestinal absorption in medically refractory autoimmune enteropathy. This observation provides clinicians with an effective treatment option in this challenging group of patients. 10.1016/j.transproceed.2020.08.007
Case Report: Severe Hypocalcemic Episodes Due to Autoimmune Enteropathy. Frontiers in endocrinology Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic disorder, associated with endocrine deficiencies and non-endocrine involvement. Gastrointestinal (GI) manifestations appear in approximately 25% of patients and are the presenting symptom in about 10% of them. Limited awareness among pediatricians of autoimmune enteropathy (AIE) caused by destruction of the gut endocrine cells in APECED patients delays diagnosis and appropriate therapy. We describe an 18-year-old female presenting at the age of 6.10 years with hypoparathyroidism, oral candidiasis and vitiligo. The clinical diagnosis of APECED was confirmed by sequencing the autoimmune regulator-encoding () gene. Several characteristics of the disease-Hashimoto's thyroiditis, Addison's disease, diabetes mellitus type 1 and primary ovarian insufficiency-developed over the years. She had recurrent episodes of severe intractable hypocalcemia. Extensive GI investigations for possible malabsorption, including laboratory analyses, imaging and endoscopy with biopsies were unremarkable. Revision of the biopsies and chromogranin A (CgA) immunostaining demonstrated complete loss of enteroendocrine cells in the duodenum and small intestine, confirming the diagnosis of AIE. Management of hypocalcemia was challenging. Only intravenous calcitriol maintained calcium in the normal range. Between hypocalcemic episodes, the proband maintained normal calcium levels, suggesting a fluctuating disease course. Repeated intestinal biopsy revealed positive intestinal CgA immunostaining. The attribution of severe hypocalcemic episodes to AIE emphasizes the need for increased awareness of this unique presentation of APECED. The fluctuating disease course and repeated intestinal biopsy showing positive CgA immunostaining support a reversible effect of GI involvement. CgA immunostaining is indicated in patients with APECED for whom all other investigations have failed to reveal an explanation for the malabsorption. 10.3389/fendo.2021.645279
Adult-Onset Autoimmune Enteropathy in an European Tertiary Referral Center. Clinical and translational gastroenterology INTRODUCTION:Adult-onset autoimmune enteropathy (AIE) is a rare cause of severe chronic diarrhea because of small intestinal villous atrophy. We report on patients with adult-onset AIE in an European referral center. METHODS:Retrospective study including patients diagnosed with AIE in the Amsterdam UMC, location VUmc, between January 2003 and December 2019. Clinical, serological, and histological features and response to treatment were reported. The specificity of antienterocyte antibodies (AEA) was evaluated by examining the prevalence of AEA in (i) controls (n = 30) and in patients with (ii) AIE (n = 13), (iii) celiac disease (CD, n = 52), (iv) refractory celiac disease type 2 (n = 18), and (v) enteropathy-associated T-cell lymphoma (EATL, n = 10). RESULTS:Thirteen AIE patients were included, 8 women (62%), median age of 52 years (range 23-73), and 6 (46%) with an autoimmune disease. AEA were observed in 11 cases (85%), but were also found in CD (7.7%), refractory celiac disease type 2 (16.7%), and EATL (20%). Ten patients (77%) were human leukocyte antigen DQ2.5 heterozygous. Total parenteral nutrition was required in 8 cases (62%). Steroids induced clinical remission in 8 cases (62%). Step-up therapy with rituximab, cyclosporine, infliximab, and cladribine in steroid-refractory patients was only moderately effective. Four patients died (31%), but 4 (31%) others are in long-term drug-free remission after receiving immunosuppressive treatment, including 1 patient who underwent autologous stem cell transplantation. DISCUSSION:Adult-onset AIE is a rare but severe enteropathy that occurs in patients susceptible for autoimmune disease. Four patients (31%) died secondary to therapy-refractory malabsorption, while immunosuppressive therapy leads to a long-lasting drug-free remission in one-third of patients. 10.14309/ctg.0000000000000387
Gastrointestinal biopsy findings of autoimmune enteropathy: a review of 25 cases. Masia Ricard,Peyton Stephen,Lauwers Gregory Y,Brown Ian The American journal of surgical pathology Autoimmune enteropathy (AIE) is a rare disorder characterized by severe diarrhea and small intestinal mucosal atrophy resulting from immune-mediated injury. It remains a challenging diagnosis because of its clinicopathologic variability. To better understand its histopathologic features, we describe the gastrointestinal biopsy findings of 25 patients, including children and adults. The most common finding on small intestinal biopsy (13/25 cases, 52%) was villous blunting, expansion of the lamina propria by mixed but predominantly mononuclear inflammation, and neutrophilic cryptitis with or without crypt microabscesses. In 5 cases (20%), the duodenum exhibited changes indistinguishable from celiac disease, with villous blunting and intraepithelial lymphocytosis. Increased crypt apoptosis with minimal inflammation, resembling acute graft-versus-host disease, was observed in 4 cases (16%). The remaining 3 cases (12%) exhibited a mixture of 2 or more of the above patterns. Mucosal abnormalities outside the small intestine were present in all 24 cases with available biopsies (100%), with the stomach most commonly affected (19/22 cases, 86%), followed by the colon (14/22, 64%) and esophagus (5/18, 28%). Findings in non-small intestinal sites were variable and included mixed active and chronic inflammation, chronic inflammation alone, intraepithelial lymphocytosis, and increased apoptosis resembling acute graft-versus-host disease. In summary, AIE most commonly presents as an active enteritis with villous blunting and expansion of the lamina propria by mixed inflammation. Mucosal abnormalities are frequently seen elsewhere in the gut. AIE may thus be better regarded as a pan-gastrointestinal autoimmune disorder, and biopsies from sites other than the small intestine may greatly facilitate its diagnosis. 10.1097/PAS.0000000000000317
[Adult-onset generalized autoimmune enteropathy involving small intestine and colon: report of a case and review of literature]. Lai Yumei,Ye Juxiang,Zhang Yan,Chang Hong,Zhang Hejun,Shi Xueying Zhonghua bing li xue za zhi = Chinese journal of pathology OBJECTIVE:To investigate the clinicopathologic features of adult-onset autoimmune enteropathy (AIE). METHODS:A case of adult-onset AIE was described along with a literature review. RESULTS:A 41-year-old male patient was admitted for intractable diarrhea for more than three months despite of any dietary restriction or anti-inflammatory therapy. Fat globule was observed by stool examination and Sudan III staining of the stool was positive. Enteroclysis showed weak movement and few plica of small intestine, while colonoscopy appeared normal. Small bowel biopsies revealed villus atrophy and increased crypt apoptotic bodies and lymphocytic infiltration in deep crypt. Although without significant surface intro-epithelial lymphocytosis, there were a large number of monocytes, lymphocytes, plasmacytes and neutrophilic granulocytes infiltrating in the lamina propria. Morphologically, the colonic mucous was similar to the small intestine although cryptitis and crypt abscess were significant in the former. Serum IgG anti-goblet cell antibody was demonstrated by indirect immunofluorescence. Other causes of diarrhea were excluded on the base of medical history, histopathology and other accessory examinations before the diagnosis of AIE was made. The patient had a complete remission after steroid treatment without recurrence for eight months during the follow-up even after steroid withdrawal for five months. CONCLUSIONS:AIE is exceedingly rare and timely diagnosis is important for successful therapy. Histological differential diagnoses should include ulcerative colitis, celiac disease, lymphocytic colitis, etc. The final diagnosis should be based on histological examination combined with the patient history, clinical manifestation, endoscopy finding and serological testing.
Recalcitrant hypocalcaemia in autoimmune enteropathy. Geyer Myfanwy,Fairchild Jan,Moore David,Moore Lynette,Henning Paul,Tham Elaine Pediatrics Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome is a monogenic disorder associated with autoimmune destruction of both endocrine and nonendocrine tissues. The classic triad includes candidiasis, hypoparathyroidism, and Addison disease. Up to 25% of patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome also have gastrointestinal manifestations, which can have an impact on the management of other aspects of the disease. The management of the case discussed was challenging because of the complex interplay between the manifestations and treatment of his hypoparathyroidism, Addison disease, and autoimmune enteropathy. Attempts at management of hypocalcemia were largely unsuccessful until the introduction of immunosuppressive therapy for autoimmune enteropathy. This case supports early consideration of immunosuppression in this condition. 10.1542/peds.2013-3308
Diffuse Autoimmune Enteropathy and Colopathy in an Adult Patient Successfully Treated With Adalimumab and a Review of the Literature. Hasan Syed Shafae,Siddiqui Nauman Saleem,Chaitanya Arudra Sri Krishna,de Las Casas Luis,Akpunonu Basil,Nawras Ali American journal of therapeutics Autoimmune enteropathy (AIE) is a rare disease that causes intractable diarrhea not responsive to a gluten free diet and must be distinguished from refractory sprue. It is associated with circulating autoantibodies against goblet cells and enterocytes. AIE mainly involves the small intestines, with very few cases reported in adults. Because of the paucity of cases, the epidemiology of the disease remains unclear, and treatment is based on the cases found in the literature. Of the 35 adult cases reported, only 4 involved the colon. Because of the low number of cases, there have been no clear recommendations on treatment modalities with most reports heavily emphasizing steroids as the mainstay of treatment. We present the case of adult female patient who developed postpartum AIE and colopathy with profuse diarrhea successfully treated with adalimumab and a review of the literature. To the best of our knowledge, this case is only the fourth case of a tumor necrosis factor alpha antagonist being used in the treatment of AIE and the first case of adalimumab being used. 10.1097/MJT.0000000000000119
Successful Treatment of Refractory Autoimmune Enteropathy With Ustekinumab. Scheid Johannes F,Misdraji Joseph,Nath Barbara J,Yarze Joseph C ACG case reports journal Autoimmune enteropathy (AIE) is a rare autoimmune disorder that has been described both in pediatric and adult patients and usually causes intractable watery diarrhea. The management of AIE is not standardized because the disease shows variable response to different immunosuppressive regimens including corticosteroids, azathioprine, cyclophosphamide, 6-mercaptopurine, tacrolimus, cyclosporine-A, infliximab, vedolizumab, and abatacept. We present a patient with adult-onset AIE and intractable high-volume diarrhea resulting in numerous hospitalizations and temporary parenteral nutrition, who is now successfully maintained on ustekinumab. Therefore, ustekinumab should be considered for further evaluation as a therapeutic option in cases of refractory AIE. 10.14309/crj.0000000000000520
Acute Flare of Adult-Onset Autoimmune Enteropathy Associated With Cyclophosphamide. Liu Jasmine,Hindi Ziad,Aziz Tariq,Albashir Siwar ACG case reports journal This is a case of adult-onset autoimmune enteropathy (AIE) in a 46-year-old man with multiple autoimmune conditions who presented with worsening disease process after receiving cyclophosphamide. We describe the investigations and management of this patient over a 6-year timeline. The diagnosis and management of AIE is challenging given the heterogeneity in clinicopathologic findings and a small number of adult case reports. We describe the current diagnostic criteria, review the literature on treatment options and outcomes, and discuss the evidence for cyclophosphamide in the treatment of AIE. Adult-onset AIE should be considered in the differential diagnosis of refractory diarrhea and weight loss. 10.14309/crj.0000000000000541
New Treatment Option for Autoimmune Enteropathy: A Rare Case of Intractable Diarrhea Treated with Vedolizumab. Robbins Gordon,Tracht Jessica,Davis Drew,Iskandar Heba ACG case reports journal Autoimmune enteropathy is an uncommon cause of chronic diarrhea rarely seen in adults. The disease is secondary to an autoimmune process in the gut that leads to villous blunting and subsequent watery diarrhea, abdominal pain, and severe weight loss. The disease has only been described in 37 adults prior to our case, and variable treatment success has been documented with steroids, immunomodulators, and TNF-α inhibitors. This case is the first to show success in treating autoimmune enteropathy with vedolizumab and provides physicians with an additional therapeutic option when limited by a patient's comorbidities and side effects of other drugs. 10.14309/crj.2018.92
Seronegative Adult Autoimmune Enteropathy in a Patient With Rheumatoid Arthritis. Lundholm Michelle D,Wanta Kaitlin,Ding Xianzhong,Palmer Lena,Abegunde Ayokunle T ACG case reports journal Autoimmune enteropathy is a rare disorder of the immune system. We present a 75-year-old woman with rheumatoid arthritis who presented with 4 months of intractable vomiting, diarrhea, and unexplained weight loss. Initial workup was negative for infection and celiac disease, but her symptoms progressed. Repeat esophagogastroduodenoscopy showed duodenal scalloping and friability. Biopsies of the duodenum and terminal ileum showed glandular destruction, epithelial apoptosis, and goblet cell depletion. Colonoscopic examination was normal, and random colon biopsies did not show evidence of microscopic colitis. She was diagnosed with autoimmune enteropathy, and treatment consisted of an extended corticosteroid taper, with the resolution of symptoms. 10.14309/crj.0000000000000239
Using Adalimumab to Treat Autoimmune Enteropathy. Trivedi Hirsh D,Shannahan Sarah E,Morrow Matthew,Peppercorn Mark A ACG case reports journal Autoimmune enteropathy is a rare condition seen in adults with limited therapeutic options available. It manifests with profuse diarrhea and malnourishment. The diagnosis is made through a combination of clinical, serologic, and histologic parameters. The cornerstone of therapy revolves around nutritional optimization and immunosuppression, most commonly in the form of corticosteroids. Alternate therapies, such as antitumor necrosis factor agents, can be considered if there is an inadequate response to steroids. We report a case of autoimmune enteropathy that was successfully treated with adalimumab, a rare treatment for an infrequent disease. 10.14309/crj.0000000000000265
Features of Adult Autoimmune Enteropathy Compared With Refractory Celiac Disease. Sharma Ayush,Choung Rok Seon,Wang Xiao Jing,Russo Pierre A,Wu Tsung-Teh,Nehra Vandana,Murray Joseph A Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association BACKGROUND & AIMS:Little is known about the features of immune-mediated non-celiac villous atrophies, such as autoimmune enteropathy (AIE). We investigated the demographic, clinical, and histologic features of adults with AIE compared to adults with refractory celiac disease type 1. We also report outcomes of treatment with open-label budesonide. METHODS:We performed a retrospective case-control of patients with AIE (n = 30) seen at the Mayo Clinic (in Rochester, Minnesota) from 2000 through 2015. Patients with refractory celiac disease type 1 who were treated with open-label budesonide served as controls (n = 42). Biopsy specimens were reviewed for all patients. We collected demographic, clinical, biochemical and histologic data from patients. We also collected data on responses to open-capsule budesonide from patients with AIE (available from 22 patients) and controls (available from 42 patients); the median duration of follow up was 28 months (range, 0-1421 months). RESULTS:Patients with AIE had a higher proportion of men (60%) and were younger (mean, 44 ± 18 years) than patients with refractory celiac disease type 1 (29% men; P = .002 and mean age, 57 ± 16 years; P = .007). A higher proportion of patients with AIE presented with chronic diarrhea (100%) and weight loss (90%) than patients with refractory celiac disease type 1 (71%; P < .001 and 71%; P = .05, respectively). Based on histologic analysis, there was no significant difference in degree of villous atrophy in intestinal tissues from patients with AIE vs controls (P = .68). However, a greater proportion of patients with RCD had increased intraepithelial lymphocytes (>40 per 100 epithelial cells in 100%) compared with patients with AIE (in 50%) (P = .003). Conventional therapy (systemic steroids) had failed in most patients with AIE (a complete clinical response was reported in only 7 patients) before treatment with open-capsule budesonide was initiated. A clinical response to open-capsule budesonide was reported for 85% of patients with AIE (50% complete response, 35% partial response) compared to 92% of controls (68% complete response, 24% partial response). CONCLUSIONS:In a retrospective study of 30 patients with AIE, followed for a median 28 months, we found this disease to have has distinct demographic, clinical, and histologic characteristics compared to refractory celiac disease type 1. Most patients with AIE (85%) have a clinical response to budesonide, all of whom were unsuccessfully treated with conventional therapies. 10.1016/j.cgh.2017.12.044
Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc The term pediatric autoimmune enteropathy was originally applied to a form of intractable diarrhea seen in children under the age of 6 months and characterized by male predominance, concurrent autoimmune-associated disorders, circulating gut autoantibodies, a lack of severe immunodeficiency and small bowel atrophy with prominent crypt apoptosis. However, recent studies have cast doubt over the specific clinicopathologic findings associated with this entity. We, therefore, collected 178 gastrointestinal biopsies from 14 patients and examined their clinical, serologic and pathologic findings. Patients at presentation ranged in age from birth to 15.9 years (median, 5.5 months; mean, 4.1 years) and included six males and eight females. All children suffered from chronic watery diarrhea and malnutrition. Concomitant-associated disorders were noted in 11 (79%) cases and included 10 (71%) with an immunodeficiency disorder and/or another autoimmune-related disease. Eleven patients (79%) were positive for anti-enterocyte antibodies. The salient findings of autoimmune enteropathy were most prominent in the small intestines and the majority (79%) of patients demonstrated villous blunting, crypt hyperplasia, mononuclear cell inflammatory expansion of the lamina propria and crypt apoptosis. The remaining (21%) patients showed marked intraepithelial lymphocytosis reminiscent of celiac disease. Further, acute cryptitis and crypt abscesses were seen in seven (50%) patients obscuring the presence of apoptosis. The absence of Paneth cells, goblet cells or both was noted in seven (50%) patients. Follow-up information was available for all patients with 13 (93%) receiving immunosuppressant therapy and demonstrating partial-to-complete response. In total, three patients died from continued diarrhea and sepsis with one decedent before treatment could be initiated. In summary, autoimmune enteropathy in children is a heterogenous disease with protean clinical and pathologic findings. Although anti-enterocyte antibodies were identified in the majority of the cases, their presence was variable and insensitive. In addition, pediatric autoimmune enteropathy was frequently encountered in the setting of immunodeficiency disorders. 10.1038/modpathol.2013.150
A case of autoimmune enteropathy with CTLA4 haploinsufficiency. Miyazaki Haruka,Hoshi Namiko,Kohashi Michitaka,Tokunaga Eri,Ku Yuna,Takenaka Haruka,Ooi Makoto,Yamamoto Nobuyuki,Uemura Suguru,Nishimura Noriyuki,Iijima Kazumoto,Jimbo Keisuke,Okano Tsubasa,Hoshino Akihiro,Imai Kohsuke,Kanegane Hirokazu,Kobayashi Ichiro,Kodama Yuzo Intestinal research Autoimmune enteropathy (AIE) is a rare disease, characterized by intractable diarrhea, villous atrophy of the small intestine, and the presence of circulating anti-enterocyte autoantibodies. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and mutations in FOXP3, which is a master gene of regulatory T cells (Tregs), are major causes of AIE. Recent studies have demonstrated that mutations in other Treg-associated genes, such as CD25 and CTLA4, show an IPEX-like phenotype. We present the case of a 13-year-old girl with CTLA4 haploinsufficiency, suffering from recurrent immune thrombocytopenic purpura and intractable diarrhea. We detected an autoantibody to the AIE-related 75 kDa antigen (AIE-75), a hallmark of the IPEX syndrome, in her serum. She responded well to a medium dose of prednisolone and a controlled dose of 6-mercaptopurine (6-MP), even after the cessation of prednisolone administration. Serum levels of the soluble interleukin-2 receptor and immunoglobulin G (IgG) were useful in monitoring disease activity during 6-MP therapy. In conclusion, autoimmune-mediated mechanisms, similar to the IPEX syndrome, may be involved in the development of enteropathy in CTLA4 haploinsufficiency. Treatment with 6-MP and monitoring of disease activity using serum levels of soluble interleukin-2 receptor and IgG is suggested for such cases. 10.5217/ir.2020.00041
[Autoimmune enteropathy in adults : A rare and difficult but relevant differential diagnosis of chronic diarrhea]. Beck A,Schulte L,Möller P Der Pathologe Autoimmune enteropathy (AIE) was originally believed to be a pediatric disease until there were increasing numbers of adult cases reported over the last 20 years. AIE is an autoimmune disease that manifests as severe chronic diarrhea.The histological hallmark is villous atrophy. Histology alone is not sufficiently sensitive and consistent. Four different histological patterns are known. There are many differential diagnoses to be considered relating to both histology and symptoms.We present the case of a young woman with fatal AIE and homozygous germline-mutation of the CLEC7A gene. The course of disease is documented in multiple intestinal biopsies, which show a morphological change over time.Histology and symptoms often resemble celiac disease. In order to recognize this rare disease early in its course there is a need for a special awareness among attending physicians and pathologists. 10.1007/s00292-020-00769-w
Neuroendocrine Cells Are Commonly Absent in the Intestinal Crypts in Autoimmune Enteropathy. Lee Hee Eun,Yuan Lin,Wu Tsung-Teh The American journal of surgical pathology The absence of neuroendocrine (NE) cells in the intestinal mucosa in autoimmune enteropathy (AIE) has been occasionally reported. However, the status of NE cells has not been studied in detail in AIE. Small bowel and colonic biopsies were retrospectively retrieved from 18 AIE patients (26 baseline [18 small bowel and 8 colon]; and 15 follow-up [11 duodenum and 4 colon] biopsies in 11 patients). Thirty-three common variable immunodeficiency (CVID) patients (30 small bowel and 16 colon), 15 inflammatory bowel disease patients (5 duodenum and 10 colon), 13 immunoglobulinA deficiency patients (13 duodenum and 5 colon), and 10 normal controls (5 colon and 5 duodenum) were selected as control groups. Histologic features (villous atrophy, intraepithelial lymphocytosis, acute inflammation, crypt apoptosis, and absence or presence of goblet cells, Paneth cells and plasma cells) were recorded. Chromogranin immunostain was performed and chromogranin-positive NE cells were counted per 10 consecutive, well-oriented crypts. On the basis of the number of chromogranin-positive NE cells, cases were graded as being absent (≤3 NE cells), markedly decreased (≤15), and intact (>15). The NE cell status correlated with histologic features. The median age of 18 AIE patients was 38.5 years (range: 11 to 74 y) and 14 patients were male. Fourteen of 18 (78%) patients showed loss (absent or markedly decreased) of NE cells in the small bowel and/or colon in the baseline biopsies including 12 (of 18) small bowel and 6 (of 8) colon biopsies. Follow-up biopsy was available in 11 patients. Six of 7 (85%) patients who showed loss of NE cells in the baseline biopsies regained NE cells in the follow-up biopsies, and 1 patient continued to show loss of NE cells. Four patients who showed intact NE cells in the baseline remained unchanged in the follow-up. Among the control groups, 3 of 33 (9%) CVID patients showed loss of NE cells. NE cells were not lost in the biopsies of all 15 and 13 patients with inflammatory bowel disease and immunoglobulinA deficiency, respectively, or the 10 normal controls. In all 41 biopsies (26 baseline plus 15 follow-up) with AIE, NE cell loss was significantly associated with increased crypt apoptosis and loss of goblet cells (P=0.001, both) but not with other histologic findings. In conclusion, our study suggests that NE cells may also be the target cells in AIE and commonly lost in the intestinal crypts in AIE, and consequently loss of NE cells can be used as an adjunct histologic feature for diagnosis of AIE. 10.1097/PAS.0000000000001516
Chronic diarrhea due to autoimmune enteropathy. Ruiz Rebollo María Lourdes,Corrales Cruz Daniel,Izquierdo Santervás Sandra,Busta Nistal Reyes,Dirá Gil Miguel,Burgueño Gómez Beatriz Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva Chronic diarrhea is a common symptom seen in the Gastroenterology clinic. Occasionally, the diagnosis is a real challenge as there are multiple entities with unremitting diarrhea as a symptom. Herein, we present a patient affected with intractable diarrhea who was transferred to our department. After many laboratory, endoscopy and radiological tests, she was diagnosed with autoimmune enteropathy (AE) and achieved clinical remission with corticosteroids and azathioprine. 10.17235/reed.2020.7218/2020
Adult autoimmune enteropathy in autoimmune hepatitis patient. Case report and literature review. Iaquinto Gaetano,Panico Luigi,Luongo Gelsomina,Tenneriello Valentina,Iaquinto Salvatore,Giardullo Nicola,Rotondi Aufiero Vera,Mazzarella Giuseppe,Rispoli Raffaella,Lucariello Angela,Perna Angelica,De Luca Antonio Clinics and research in hepatology and gastroenterology Autoimmune enteropathy (AIE) is a rare disease characterized by prolonged diarrhea, vomiting and weight loss; although it is mainly a rare pediatric disease, over the years a number of adults have also been found to be affected. In this study, we present a case report of a 73-year-old woman with a history of autoimmune hepatitis, antinuclear (ANA) and positive anti-enterocyte antibodies (AEA), who has suffered two months of intractable diarrhea, nausea, anorexia and severe weight loss. The histological examination of the endoscopic duodenal mucosa biopsies revealed severe shortening and flattening of the villi, resulting in mucosal atrophy. The immunohistochemical study revealed a polymorphic lymphoid population, exhibiting a B cell (CD20+) phenotype in follicles and a T cell phenotype (CD3+) in the diffuse component within the lamina propria. Our patient had a complete recovery after two weeks of taking prednisone and following a gluten-rich diet. To our knowledge this is the first case of autoimmune enteropathy in adults with ANA and AEA 7 years after a diagnosis of autoimmune hepatitis. To date, the patient is still in clinical remission on a low dose of orally administered predinisone without any additional immunosuppression. 10.1016/j.clinre.2021.101673
Clinical manifestations and gastrointestinal pathology in 40 patients with autoimmune enteropathy. Villanacci Vincenzo,Lougaris Vassilios,Ravelli Alberto,Buscarini Elisabetta,Salviato Tiziana,Lionetti Paolo,Salemme Marianna,Martelossi Stefano,De Giacomo Costantino,Falchetti Diego,Pelizzo Gloria,Bassotti Gabrio Clinical immunology (Orlando, Fla.) Autoimmune enteropathy (AIE) is a rare condition that may affect pediatric and adult patients, frequently associated with primary immunodeficiencies. We performed a retrospective study on clinical and histological findings from 40 AIE patients. Histological presentation showed a prevalent celiac disease pattern (50%), followed by the mixed pattern (35%), independently of age, chronic active duodenitis (10%), and GVHD-like pattern (5%). Patients with primary immunodeficiencies (24/40) presented mainly with the celiac disease pattern (72.2% versus 22.2%; p < .0001), while patients without primary immunodeficiencies presented with a mixed histological pattern (61.1% versus 13.6%; p < .0001). Our study shows that the prevalent histological presentation is the celiac disease-like pattern, independently of age, and, for the first time, that the histological presentation of AIE differs significantly between patients with and without primary immunodeficiencies. These findings may be helpful for more precise and timely diagnosis and management of this rare disorder. 10.1016/j.clim.2019.07.001
Seronegative autoimmune enteropathy with duodenal sparing and colonic clues in an adult female. Chong Albert,Kashani Amir,Ansstas Michael,Jamil Laith,Guindi Maha Clinical journal of gastroenterology Autoimmune enteropathy (AIE) is a rare immune disorder of the gut seldom found in adults and characterized by uncontrollable diarrhea resulting in malabsorption. While AIE is known to be pan-enteric, virtually all cases have presented with altered duodenal histology following known patterns with or without macroscopic change. We describe a unique case of seronegative AIE lacking typical duodenal manifestations in a 43-year-old female. To our knowledge, this is the first report of AIE lacking usual duodenal histologic changes, which resulted in missed diagnosis for years. Ultimately, crypt epithelial apoptosis, mononuclear inflammation of the lamina propria, and goblet cell loss of intestinal mucosa besides the duodenum clinched the diagnosis of AIE. Colonic histologic abnormalities consistent with AIE in the setting of diarrhea with malnutrition despite duodenal sparing should prompt suspicion for AIE given the pan-enteric nature of this disease. 10.1007/s12328-020-01336-9
A Review of Autoimmune Enteropathy and Its Associated Syndromes. Chen Charles B,Tahboub Farah,Plesec Thomas,Kay Marsha,Radhakrishnan Kadakkal Digestive diseases and sciences Autoimmune enteropathy is an extremely rare condition characterized by an abnormal intestinal immune response which typically manifests within the first 6 months of life as severe, intractable diarrhea that does not respond to dietary modification. Affected individuals frequently present with other signs of autoimmunity. The diagnosis is made based on a characteristic combination of clinical symptoms, laboratory studies, and histological features on small bowel biopsy. Autoimmune enteropathy is associated with a number of other conditions and syndromes, most notably immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome and autoimmune polyglandular syndrome type 1 (APS-1). Diagnosis and treatment is challenging, and further research is needed to better understand the pathogenesis, disease progression, and long-term outcomes of these conditions. 10.1007/s10620-020-06540-8